In the bone regeneration process, once the balance of the bone remodeling is broken, the bone resorption of the osteoclasts is dominated over bone formation of the osteoblasts, the bone remodeling would be imbalanced. As a result, the osteocytes would decrease, osteopenia or bone mineral density decrease to induce lots of bone disease, such as osteoporosis, periodontitis or osteoarthritis.
The osteoclasts origins from hematopoietic precursor cells. Further, the Macrophage-Colony Stimulating Factor (M-CSF) secreted by osteoblast and Receptor Activator of Nuclear factor Kappa B Ligand (RANK. L) would combine with the c-Fms and RANK on the cell membrane of the osteoclast precursor cells, and induce the secretion of tartrate-resistant acid phosphatase (TRAP), integrin b3 expression, and actin ring formation, etc. These changes of protein activity and cell morphology would enhance the osteoclasts motility and help the osteoclasts adhere on the bone surface. On the other hand, the expression of cathepsin K matrix metalloproteinase-9 (MMP-9), dendritic cell-specific transmembrane protein (DC-STAMP), ATPase, H+ transporting lysosomal V0 subunit D2(ATP6V0D2) would induce the osteoclast precursor cells differentiate into a hung matured (diameter is 20-100 mm) multinucleated cells (MNCs) (containing 4-20 nucleus), which also have the bone resorption function.
The osteoblasts would secret M-CSF and RANKL, which induce the osteocytes growth and differentiation, and would also secret the osteoprotegerin (OPG). OPG would associate with RANKL to prevent the association of RANKL and RANK, so as to prevent the formation of osteoclasts and inhibit the formation of osteoclasts, to decrease the bone resorption; besides, OPG would involve in the osteoclast apoptosis.